The objectives of this program are to investigate the biomechanical behavior of red blood cells, white blood cells, endothelial cells, smooth muscle cells and other components of the vasculature; to study the micromechanics and molecular mechanisms of cardiovascular cell-cell interactions; and to assess the biomechanical and molecular basis of vascular function and microcirculatory dynamics in health and disease. The rheological properties of normal and abnormal blood cells, endothelial cells and smooth muscle cells will be studied by micromechanical techniques. The experimental results will be subjected to computational analysis and serve as the basis of theoretical modeling. These findings will be correlated with the molecular organization of the cell membrane, especially the membrane proteins. The Program will employ a multidisciplinary, systematic approach involving parallel experimental and theoretical investigations, which cover the spectrum ranging from molecular biology to the in vivo circulation. The specific aims of research are (a) to investigate the rheological properties, molecular dynamics, and interactions of cells in the circulation, including both the blood and the vascular wall. (b) to elucidate the interrelationships between the molecular organization of these cells with their biomechanical behavior, and (c) to establish the functional roles of the biomechanics of blood cells, blood vessels and microcirculation in health and disease. The research projects will be supported by core facilities in the Administrative Office, Cell and Tissue Culture Facilities, Computer Modeling and Image Processing Facilities, Instrumentation Laboratory, and Ultrastructure Laboratory. The coordinated effort is aimed at elucidating the molecular basis and physiological roles of the biomechanical behavior of blood cells, endothelial cells and vascular smooth muscle cells, as well as the responses of these cells to mechanical force. The ultimate goal is to provide the fundamental knowledge needed to improve diagnosis and treatment of cardiovascular and blood diseases.